Inflammation-Triggered Enlargement of Choroid Plexus in Subacute COVID-19 Patients with Neurological Symptoms.

OBJECTIVE: To investigate whether choroid plexus volumes in subacute coronavirus disease 2019 (COVID-19) patients with neurological symptoms could indicate inflammatory activation or barrier dysfunction and assess their association with clinical data. METHODS: Choroid plexus volumes were measured in 28 subacute COVID-19 patients via cerebral magnetic resonance imaging (MRI), compared with those in infection-triggered non-COVID-19 encephalopathy patients (n = 25), asymptomatic individuals after COVID-19 (n = 21), and healthy controls (n = 21). Associations with inflammatory serum markers (peak counts of leukocytes, C-reactive protein [CRP], interleukin 6), an MRI-based marker of barrier dysfunction (CSF volume fraction [V-CSF]), and clinical parameters like olfactory performance and cognitive scores (Montreal Cognitive Assessment) were investigated. RESULTS: COVID-19 patients showed significantly larger choroid plexus volumes than control groups (p < 0.001, η2 = 0.172). These volumes correlated significantly with peak leukocyte levels (p = 0.001, Pearson's r = 0.621) and V-CSF (p = 0.009, Spearman's rho = 0.534), but neither with CRP nor interleukin 6. No significant correlations were found with clinical parameters. INTERPRETATION: In patients with subacute COVID-19, choroid plexus volume is a marker of central nervous system inflammation and barrier dysfunction in the presence of neurologic symptoms. The absence of plexus enlargement in infection-triggered non-COVID-19 encephalopathy suggests a specific severe acute respiratory syndrome coronavirus 2 effect. This study also documents an increase in choroid plexus volume for the first time as a parainfectious event. ANN NEUROL 2024.

Concurrent inflammation-related brain reorganization in multiple sclerosis and depression.

BACKGROUND: Neuroinflammation affects brain tissue integrity in multiple sclerosis (MS) and may have a role in major depressive disorder (MDD). Whether advanced magnetic resonance imaging characteristics of the gray-to-white matter border serve as proxy of neuroinflammatory activity in MDD and MS remain unknown. METHODS: We included 684 participants (132 MDD patients with recurrent depressive episodes (RDE), 70 MDD patients with a single depressive episode (SDE), 222 MS patients without depressive symptoms (nMS), 58 MS patients with depressive symptoms (dMS), and 202 healthy controls (HC)). 3 T-T1w MRI-derived gray-to-white matter contrast (GWc) was used to reconstruct and characterize connectivity alterations of GWc-covariance networks by means of modularity, clustering coefficient, and degree. A cross-validated support vector machine was used to test the ability of GWc to stratify groups according to their depression symptoms, measured with BDI, at the single-subject level in MS and MDD independently. FINDINGS: MS and MDD patients showed increased modularity (ANOVA partial-η2 = 0.3) and clustering (partial-η2 = 0.1) compared to HC. In the subgroups, a linear trend analysis attested a gradient of modularity increases in the form: HC, dMS, nMS, SDE, and RDE (ANOVA partial-η2 = 0.28, p < 0.001) while this trend was less evident for clustering coefficient. Reduced morphological integrity (GWc) was seen in patients with increased depressive symptoms (partial-η2 = 0.42, P < 0.001) and was associated with depression scores across patient groups (r = -0.2, P < 0.001). Depressive symptoms in MS were robustly classified (88 %). CONCLUSIONS: Similar structural network alterations in MDD and MS exist, suggesting possible common inflammatory events like demyelination, neuroinflammation that are caught by GWc analyses. These alterations may vary depending on the severity of symptoms and in the case of MS may elucidate the occurrence of comorbid depression.

Cortical and subcortical microstructure integrity changes after repetitive transcranial magnetic stimulation therapy in cocaine use disorder and relates to clinical outcomes.

Cocaine use disorder (CUD) is a worldwide public health condition that is suggested to induce pathological changes in macrostructure and microstructure. Repetitive transcranial magnetic stimulation (rTMS) has gained attention as a potential treatment for CUD symptoms. Here, we sought to elucidate whether rTMS induces changes in white matter (WM) microstructure in frontostriatal circuits after 2 weeks of therapy in patients with CUD and to test whether baseline WM microstructure of the same circuits affects clinical improvement. This study consisted of a 2-week, parallel-group, double-blind, randomized controlled clinical trial (acute phase) (sham [n = 23] and active [n = 27]), in which patients received two daily sessions of rTMS on the left dorsolateral prefrontal cortex (lDLPFC) as an add-on treatment. T1-weighted and high angular resolution diffusion-weighted imaging (DWI-HARDI) at baseline and 2 weeks after served to evaluate WM microstructure. After active rTMS, results showed a significant increase in neurite density compared with sham rTMS in WM tracts connecting lDLPFC with left and right ventromedial prefrontal cortex (vmPFC). Similarly, rTMS showed a reduction in orientation dispersion in WM tracts connecting lDLPFC with the left caudate nucleus, left thalamus, and left vmPFC. Results also showed a greater reduction in craving Visual Analogue Scale (VAS) after rTMS when baseline intra-cellular volume fraction (ICVF) was low in WM tracts connecting left caudate nucleus with substantia nigra and left pallidum, as well as left thalamus with substantia nigra and left pallidum. Our results evidence rTMS-induced WM microstructural changes in fronto-striato-thalamic circuits and support its efficacy as a therapeutic tool in treating CUD. Further, individual clinical improvement may rely on the patient's individual structural connectivity integrity.

Subthalamic stimulation modulates context-dependent effects of beta bursts during fine motor control.

Increasing evidence suggests a considerable role of pre-movement beta bursts for motor control and its impairment in Parkinson's disease. However, whether beta bursts occur during precise and prolonged movements and if they affect fine motor control remains unclear. To investigate the role of within-movement beta bursts for fine motor control, we here combine invasive electrophysiological recordings and clinical deep brain stimulation in the subthalamic nucleus in 19 patients with Parkinson's disease performing a context-varying task that comprised template-guided and free spiral drawing. We determined beta bursts in narrow frequency bands around patient-specific peaks and assessed burst amplitude, duration, and their immediate impact on drawing speed. We reveal that beta bursts occur during the execution of drawing movements with reduced duration and amplitude in comparison to rest. Exclusively when drawing freely, they parallel reductions in acceleration. Deep brain stimulation increases the acceleration around beta bursts in addition to a general increase in drawing velocity and improvements of clinical function. These results provide evidence for a diverse and task-specific role of subthalamic beta bursts for fine motor control in Parkinson's disease; suggesting that pathological beta bursts act in a context dependent manner, which can be targeted by clinical deep brain stimulation.

Harnessing the frontal aslant tract's structure to assess its involvement in cognitive functions: new insights from 7-T diffusion imaging.

The first therapeutical goal followed by neurooncological surgeons dealing with prefrontal gliomas is attempting supramarginal tumor resection preserving relevant neurological function. Therefore, advanced knowledge of the frontal aslant tract (FAT) functional neuroanatomy in high-order cognitive domains beyond language and speech processing would help refine neurosurgeries, predicting possible relevant cognitive adverse events and maximizing the surgical efficacy. To this aim we performed the recently developed correlational tractography analyses to evaluate the possible relationship between FAT's microstructural properties and cognitive functions in 27 healthy subjects having ultra-high-field (7-Tesla) diffusion MRI. We independently assessed FAT segments innervating the dorsolateral prefrontal cortices (dlPFC-FAT) and the supplementary motor area (SMA-FAT). FAT microstructural robustness, measured by the tract's quantitative anisotropy (QA), was associated with a better performance in episodic memory, visuospatial orientation, cognitive processing speed and fluid intelligence but not sustained selective attention tests. Overall, the percentual tract volume showing an association between QA-index and improved cognitive scores (pQACV) was higher in the SMA-FAT compared to the dlPFC-FAT segment. This effect was right-lateralized for verbal episodic memory and fluid intelligence and bilateralized for visuospatial orientation and cognitive processing speed. Our results provide novel evidence for a functional specialization of the FAT beyond the known in language and speech processing, particularly its involvement in several higher-order cognitive domains. In light of these findings, further research should be encouraged to focus on neurocognitive deficits and their impact on patient outcomes after FAT damage, especially in the context of glioma surgery.

The association between posterior resting-state EEG alpha rhythms and functional MRI connectivity in older adults with subjective memory complaint.

Resting-state eyes-closed electroencephalographic (rsEEG) alpha rhythms are dominant in posterior cortical areas in healthy adults and are abnormal in subjective memory complaint (SMC) persons with Alzheimer's disease amyloidosis. This exploratory study in 161 SMC participants tested the relationships between those rhythms and seed-based resting-state functional magnetic resonance imaging (rs-fMRI) connectivity between thalamus and visual cortical networks as a function of brain amyloid burden, revealed by positron emission tomography and cognitive reserve, measured by educational attainment. The SMC participants were divided into 4 groups according to 2 factors: Education (Edu+ and Edu-) and Amyloid burden (Amy+ and Amy-). There was a statistical interaction (p < 0.05) between the two factors, and the subgroup analysis using estimated marginal means showed a positive association between the mentioned rs-fMRI connectivity and the posterior rsEEG alpha rhythms in the SMC participants with low brain amyloidosis and high CR (Amy-/Edu+). These results suggest that in SMC persons, early Alzheimer's disease amyloidosis may contrast the beneficial effects of cognitive reserve on neurophysiological oscillatory mechanisms at alpha frequencies and connectivity between the thalamus and visual cortical networks.

Multiple sclerosis endophenotypes identified by high-dimensional blood signatures are associated with distinct disease trajectories.

One of the biggest challenges in managing multiple sclerosis is the heterogeneity of clinical manifestations and progression trajectories. It still remains to be elucidated whether this heterogeneity is reflected by discrete immune signatures in the blood as a surrogate of disease pathophysiology. Accordingly, individualized treatment selection based on immunobiological principles is still not feasible. Using two independent multicentric longitudinal cohorts of patients with early multiple sclerosis (n = 309 discovery and n = 232 validation), we were able to identify three distinct peripheral blood immunological endophenotypes by a combination of high-dimensional flow cytometry and serum proteomics, followed by unsupervised clustering. Longitudinal clinical and paraclinical follow-up data collected for the cohorts revealed that these endophenotypes were associated with disease trajectories of inflammation versus early structural damage. Investigating the capacity of immunotherapies to normalize endophenotype-specific immune signatures revealed discrete effect sizes as illustrated by the limited effect of interferon-ß on endophenotype 3-related immune signatures. Accordingly, patients who fell into endophenotype 3 subsequently treated with interferon-ß exhibited higher disease progression and MRI activity over a 4-year follow-up compared with treatment with other therapies. We therefore propose that ascertaining a patient's blood immune signature before immunomodulatory treatment initiation may facilitate prediction of clinical disease trajectories and enable personalized treatment decisions based on pathobiological principles.